Insular and anterior cingulate cortex deep stimulation for central neuropathic pain

Journal: Neurourology 92:e2165-e2175(2019)

Authors: R Galhardoni, V Aparecida da Silva, L García-Larrea,C Dale,A.F Baptista, L.M Barbosa,... D Ciampi de Andrade


Central neuropathic pain (CNP) is caused by a lesion or disease of the somatosensory pathways in the CNS. Unfortunately, attempts to control CNP have been marked by refractoriness and unsuccessfulness. rTMStargeted to the primary motor cortex (M1) has been successfully used to relieve several chronic pain syndromes such as fibromyalgia and peripheral neuropathic pain. Nevertheless, a significant proportion of patients fail to respond to M1 stimulation, and the analgesic effects of superficial rTMS, regardless of the target chosen, have not been clearly demonstrated for patients with CNP.Accumulating evidence have implicated deeper brain structures such as the anterior cingulate cortex (ACC) and posterior superior insula (PSI) in the processing of pain.


To compare the analgesic effects of stimulation of the ACC or the PSI against sham deep rTMSin patients with CNP after stroke or spinal cord injury in a randomized, double-blinded, sham-controlled, 3-arm parallel study.


Participants were randomly allocated into the active PSI-rTMS, ACC-rTMS, sham-PSI-rTMS, or sham-ACC-rTMS arms. Stimulations were performed for 12 weeks, and a comprehensive clinical and pain assessment, psychophysics, and cortical excitability measurements were per-formed at baseline and during treatment. The main outcome of the study was pain intensity (numeric ratingscale [NRS]) after the last stimulation session.


Ninety-eight patients (age 55.02 ± 12.13 years) completed the study. NRS score was not significantly different between groups at the end of the study. Active rTMS treatments had no significant effects on pain interference with daily activities, pain dimensions, neuropathic pain symptoms, mood, medication use, cortical excitability measurements, or quality of life. Heat pain threshold was significantly increased after treatment in the PSI-Deep TMS™ group from baseline (1.58, 95% confidence interval [CI] 0.09–3.06]) compared to sham-Deep TMS (−1.02, 95% CI −2.10 to 0.04, p = 0.014), and ACC-Deep TMS caused a significant decrease in anxiety scores (−2.96, 95% CI −4.1 to −1.7]) compared to sham-Deep TMS (−0.78, 95% CI −1.9 to 0.3; p = 0.018).


ACC-and PSI-Deep TMS were not different from sham-Deep TMS for pain relief in CNP despite a significant antinociceptive effect after insular stimulation and anxiolytic effects of ACC-Deep TMS. These results showed that the different dimensions of pain can be modulated in humans noninvasively by directly stimulating deeper SNC cortical structures without necessarily affecting clinical pain per se.

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